Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Galanin, a neuroendocrine peptide with a multitude of functions, binds to and acts on specific G-protein coupled receptors. Only one galanin receptor subtype, GalRI, has been cloned so far, although pharmacological evidence suggests the presence of more than one galanin receptor subtype. These receptors mediate via different Gi/Go-proteins the inhibition of adenylyl cyclase, opening of K+-channels and closure of Ca2+-channels. Galanin inhibits secretion of insulin, acetylcholine, serotonin and noradrenaline, while it stimulates prolactin and growth hormone release. Determination of structural components of galanin receptors required for binding of the peptide ligand as carried out recently will facilitate the screening and design of molecules specifically acting on galaninergic systems with therapeutic potential in Alzheimer's disease, feeding disorders, pain and depression.
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PMID:Galanin receptors: involvement in feeding, pain, depression and Alzheimer's disease. 912 74

As the population ages, Alzheimer's disease and depression are becoming increasingly common concerns for primary care physicians. While the comorbidity of Alzheimer's disease and depression presents a complex diagnostic and management challenge, treatment can improve the patient's quality of life. Changes in functional status, complaints of pain and fluctuations in mental status may signify the onset of depression in a patient with dementia. Because of differences in treatment, it is important to separate depression from other disruptions in behavior. Unfortunately, screening tools for depression and cognitive function are of limited usefulness in patients with Alzheimer's disease. Improvement with antidepressant therapy is often diagnostic. The caregiver plays a large role in assisting with the diagnosis and assessing the effectiveness of therapy.
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PMID:Comorbid disease in geriatric patients: dementia and depression. 919 55

Relatively low use of nonsteroidal anti-inflammatory drugs (NSAIDs) and other analgesics has been noted in patients with probable Alzheimer disease (AD). Although this finding has been explained by a decline in patients' capacities to communicate about pain, self-report on pain of cognitively impaired elderly have been shown to be just as reliable as those of cognitively unimpaired elderly. However, previously published studies were aimed primarily at quantifying pain. Considering the various limbic areas affected in AD, a change also in the more qualitative, affective component of pain might be the cause of the low use of analgesics. Because affective disorders are highest in the early and middle stages of AD and decrease in the final stage, it was hypothesized in the present study that not only would the number of AD patients using analgesics would be lower than among a control group but, moreover, analgesic use would be lower in the early and middle stages of AD than in the final stage. The hypothesis was tested by comparing drug use (NSAIDs and analgesic non-NSAIDs) among 66 AD patients with that among 70 elderly people without dementia. The percentage of AD patients using analgesics was indeed significantly lower than among controls, but drug use was not dependent on the stage of AD. Consequently, our findings only partly support the hypothesis.
Alzheimer Dis Assoc Disord 1997 Sep
PMID:Is decreased use of analgesics in Alzheimer disease due to a change in the affective component of pain? 930 3

The Geriatric Depression Scale (GDS) is intended for easy measurement of symptoms of depression in elderly patients. The scale initially had 30 items but was reduced to a 15-item scale (GDS-15). This scale was translated into Swedish. However, five items were added: insomnia, anxiety, panic, aches and pain, and hypochondria. A total of 1002 elderly patients were rated by a research nurse using this scale. The results showed that 13.3% of the patients were considered to have affective disorders. The introduction of selective serotonin reuptake inhibitors has been of great importance for elderly patients, as these patients have difficulty in tolerating traditional tricyclic antidepressants. In a study of 133 elderly depressed patients, including those with somatic disorders and dementia, citalopram was tested. This drug provided significantly greater improvement than placebo. In another, inter-Nordic study, including 98 patients, citalopram was tested in patients with Alzheimer-type dementia. Depressed mood, and also other emotional disturbances, improved in these patients. Ratings have shown that in victims of Alzheimer-type dementia and vascular dementia, about 80% suffer from emotional disturbances. Drugs that influence both serotonin and noradrenaline metabolism have been introduced recently; these are of great interest in the treatment of elderly people.
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PMID:Recognition and management of depression in the elderly. 947 38

The G protein Go is highly expressed in neurons and mediates effects of a group of rhodopsin-like receptors that includes the opioid, alpha2-adrenergic, M2 muscarinic, and somatostatin receptors. In vitro, Go is also activated by growth cone-associated protein of Mr 43,000 (GAP43) and the Alzheimer amyloid precursor protein, but it is not known whether this occurs in intact cells. To learn about the roles that Go may play in intact cells and whole body homeostasis, we disrupted the gene encoding the alpha subunits of Go in embryonic stem cells and derived Go-deficient mice. Mice with a disrupted alphao gene (alphao-/- mice) lived but had an average half-life of only about 7 weeks. No Goalpha was detectable in homogenates of alphao-/- mice by ADP-ribosylation with pertussis toxin. At the cellular level, inhibition of cardiac adenylyl cyclase by carbachol (50-55% at saturation) was unaffected, but inhibition of Ca2+ channel currents by opioid receptor agonist in dorsal root ganglion cells was decreased by 30%, and in 25% of the alphao-/- cells examined, the Ca2+ channel was activated at voltages that were 13.3 +/- 1.7 mV lower than in their counterparts. Loss of alphao was not accompanied by appearance of significant amounts of active free betagamma dimers (prepulse test). At the level of the living animal, Go-deficient mice are hyperalgesic (hot-plate test) and display a severe motor control impairment (falling from rotarods and 1-inch wide beams). In spite of this deficiency, alphao-/- mice are hyperactive and exhibit a turning behavior that has them running in circles for hours on end, both in cages and in open-field tests. Except for one, all alphao-/- mice turned only counterclockwise. These findings indicate that Go plays a major role in motor control, in motor behavior, and in pain perception and also predict involvement of Go in Ca2+ channel regulation by an unknown mechanism.
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PMID:Multiple neurological abnormalities in mice deficient in the G protein Go. 950 Dec 52

Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor selectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In addition to the induction of COX-2 in inflammatory lesions, it is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are also important in ovulation and in the birth process. The discovery of COX-2 has made possible the design of drugs that reduce inflammation without removing the protective PGs in the stomach and kidney made by COX-1. These highly selective COX-2 inhibitors may not only be anti-inflammatory but may also be active in colon cancer and Alzheimer's disease.
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PMID:Cyclooxygenases 1 and 2. 959 50

Nerve growth factor (NGF) is important for the survival and maintenance of central cholinergic neurons, a signalling system impaired in Alzheimer's disease. We have treated 3 patients with Alzheimer's disease with a total of 6.6 mg NGF administered continuously into the lateral cerebral ventricle for 3 months in the first 2 patients and a total of 0.55 mg for 3 shorter periods in the third patient. The patients were extensively evaluated with clinical, neuropsychological, neurophysiological and neuroradiological techniques. Three months after the NGF treatment ended, a significant increase in nicotine binding was found in several brain areas in the first 2 patients and in the hippocampus in the third patient as studied by positron emission tomography. A clear cognitive amelioration could not be demonstrated, although a few neuropsychology tests showed slight improvements. The amount of slow-wave cortical activity as studied by electroencephalography was reduced in the first 2 patients. Two negative side effects occurred with NGF treatment: first, a dull, constant back pain was observed in all 3 patients, which in 1 patient was aggravated by axial loading resulting in sharp, shooting pain of short duration. When stopping the NGF infusion, the pain disappeared within a couple of days. Reducing the dose of NGF lessened the pain. Secondly, a marked weight reduction during the infusion with a clear weight gain after ending the infusion was seen in the first 2 patients. We conclude from this limited trial that, while long-term intracerebroventricular NGF administration may cause certain potentially beneficial effects, the intraventricular route of administration is also associated with negative side effects that appear to outweigh the positive effects of the present protocol. Alternative routes of administration, and/or lower doses of NGF, perhaps combined with low doses of other neurotrophic factors, may shift this balance in favor of positive effects.
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PMID:Intracerebroventricular infusion of nerve growth factor in three patients with Alzheimer's disease. 970 76

We present updated information on a previously reported kindred with an autosomal dominant disorder variably expressed as indifference to pain, dementia, and ataxia. Additional clinical and radiological information is presented, as are autopsy results form the index case. In addition to evidence of Alzheimer's disease, the autopsy revealed bilateral thalamic gliosis, which may be a neuroanatomic substrate for the indifference to pain seen in this patient. To our knowledge, this is the first reported association of thalamic gliosis and indifference to pain.
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PMID:A unique autosomal dominant disorder with indifference to pain: clinicopathologic correlation of indifference to pain and thalamic gliosis. 974 71

Ovarian steroids produce a variety of effects on the brain, influencing diverse nonreproductive processes such as cognitive function, motor activity, seizure susceptibility, and pain sensitivity, as well as pathological processes such as Parkinson's disease and Alzheimer's disease. Studies of ovarian hormone effects on animal brains have revealed a wide array of neurochemical and structural effects of ovarian steroids, which are reviewed in this article. These studies provide a foundation for understanding hormone effects on mood, behavior, and cognition in the menstrual cycle, during reproductive transitions and in depressive illness.
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PMID:Clinically relevant basic science studies of gender differences and sex hormone effects. 980 50

Nonsteroidal anti-inflammatory drugs (NSAIDs) produce their therapeutic activities through inhibition of cyclooxygenase (COX), the enzyme that makes prostaglandins (PGs). They share, to a greater or lesser degree, the same side effects, including gastric and renal toxicity. Recent research has shown that there are at least two COX isoenzymes. COX-1 is constitutive and makes PGs that protect the stomach and kidney from damage. COX-2 is induced by inflammatory stimuli, such as cytokines, and produces PGs that contribute to the pain and swelling of inflammation. Thus, selective COX-2 inhibitors should be anti-inflammatory without side effects on the kidney and stomach. Of course, selective COX-2 inhibitors may have other side effects and perhaps other therapeutic potential. For instance, COX-2 (and not COX-1) is thought to be involved in ovulation and in labor. In addition, the well-known protective action of aspirin on colon cancer may be through an action on COX-2, which is expressed in this disease. Moreover, NSAIDs delay the progress of Alzheimer's disease. Thus, selective COX-2 inhibitors may demonstrate new important therapeutic benefits as anticancer agents, as well as in preventing premature labor and perhaps even retarding the progression of Alzheimer's disease.
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PMID:Anti-inflammatory drugs and their mechanism of action. 983 28


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